Hair regrowth in alopecia areata and re-pigmentation in vitiligo in response to treatment: Commonalities and differences.

Both alopecia areata (AA) and vitiligo share common pathogenesis involving, interferon-γ (IFN-γ) and interleukin-15 (IL-15) signalling pathways that activate cytotoxic CD8+ T lymphocytes. These shared mechanisms may explain why both diseases respond to currently available treatments (e.g. topical/systemic corticosteroid) and emerging treatment modalities. As compared with the speed of re-pigmentation in vitiligo lesions, the regeneration of pigmented terminal hair follicles in AA lesions appears fast in response to treatments targeting the inhibition of the Janus kinases (JAKs) and other kinases. We summarize the commonalities and differences between AA and vitiligo focusing on the treatment modalities, followed by recent findings associated with hair follicle stem cells (HFSC) in hair bulge (HBg) and melanocyte stem cells (McSC) in HBg and hair germ (HGm). We then discuss how HFSC and HGm-McSC are involved in the initiation of anagen phase, followed by pigmented terminal hair regrowth in the recovering AA lesions in association with immunology. We also discuss how HBg-McSC contribute to the migration of fully dendritic mature melanocytes into interfollicular epidermis and the equal distribution of melanin in recovering vitiligo lesions. Finally, we present four hypotheses to elucidate the delayed distribution of melanin by mature melanocytes in depigmented vitiligo lesions from the aspects of stem cell biology, as compared with quick hair recovery in AA: (1) McSC are less abundant than HFSC. (2) McSC require a long travel, whereas HFSC reside close to hair regeneration trigger point. (3) Keratinocyte scaffold to accept melanin is not well preserved, whereas scaffold for hair regrowth is well preserved. (4) Inhibitors targeting JAKs and other kinases have less direct effects on melanocyte proliferation and differentiation in vitiligo than hair regrowth in AA. Our review provides an overview of treatment modalities and bridges the gap between scientific advancement and clinical practice in AA and vitiligo management.

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-ß (TGF-ß), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/ß-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Role of Innate Immunity in Allergic Contact Dermatitis: An Update.

Our understanding of allergic contact dermatitis mechanisms has progressed over the past decade. Innate immune cells that are involved in the pathogenesis of allergic contact dermatitis include Langerhans cells, dermal dendritic cells, macrophages, mast cells, innate lymphoid cells (ILCs), neutrophils, eosinophils, and basophils. ILCs can be subcategorized as group 1 (natural killer cells; ILC1) in association with Th1, group 2 (ILC2) in association with Th2, and group 3 (lymphoid tissue-inducer cells; ILC3) in association with Th17. Pattern recognition receptors (PRRs) including toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) in innate immune cells recognize damage-associated molecular patterns (DAMPs) and cascade the signal to produce several cytokines and chemokines including tumor necrosis factor (TNF)-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-1ß, IL-4, IL-6, IL-12, IL-13, IL-17, IL-18, and IL-23. Here we discuss the recent findings showing the roles of the innate immune system in allergic contact dermatitis during the sensitization and elicitation phases.